Discovering the Mechanistic Basis of Individual Differences in Sensory Representation and their Effects on Preference Behavior

发现感觉表征个体差异的机制基础及其对偏好行为的影响

• 批准号: 1557913
• 负责人: Benjamin de Bivort
• 金额: $ 67.5万
• 依托单位: Harvard University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1557913&HistoricalAwards=false
• 关键词: Discovering; Mechanistic; Basis; Individual; Differences

Why individuals behave differently from one another is an enduring question in behavioral neuroscience. Every individual is a product of unique genetics, environment, experience and developmental contingencies. How these differences play out to produce individual behavior is currently unknown. This project aims to study the origins of individuality in behavior using the genetic model system Drosophila melanogaster, which permits holding genetics, environment and experience constant across individuals. Nevertheless behavioral diversity on odor-evoked behaviors is abundant in these experimental populations. The molecular and neural circuit mechanisms underlying these individual differences will be investigated using the tools of modern behavioral neuroscience, including high-throughput behavioral testing, pharmacological manipulation to identify critical neuromodulatory effects and neurotransmitters, and imaging to record neural activity. Preliminary evidence suggests that each individual encodes odor information differently. That is, behavioral differences may arise because each individual senses its olfactory environment differently. The mechanisms underlying these differences in stimulus encoding will be the focus of investigation. The principles uncovered are likely applicable in humans as well, given the commonalities of molecular biology across animal species. In order to broadly communicate these principles, and encourage student STEM engagement, the PI will collaborate with the DNA Learning Center of Cold Spring Harbor Laboratory to develop and distribute odor preference kits for high school students. These will allow students to measure variation in their own odor preference and investigate its origin in genetic differences in olfactory receptors.The objective of this project is to identify the neural underpinnings of the intragenotypic variability in odor-evoked behavior using a uniquely accessible system - the early olfactory circuit of the fruit fly, Drosophila melanogaster. Building on tools developed in their laboratory, a combined approach of behavioral and neurophysiological characterization will be used to determine the: 1) degree of idiosyncrasy in flies' odor preferences, 2) ways in which odor coding varies between individuals, and 3) behavioral consequences of this neurophysiological variation. In flies, the olfactory system is coarsely hardwired, with neurons that are anatomically and genetically identifiable across different individuals. Despite this stereotypy, individual odor preference is quite variable across flies - as in humans. Likewise, the neural coding of odor varies between flies. The relationship between these dimensions of variation is unknown, but can be elucidated by identifying neural coding features that predict behavioral tendencies. First, their behavioral assay will be extended to measure multidimensional odor preferences of individual flies. Second, subcellular-resolution functional imaging will quantify across-fly variation in neural coding in olfactory sub-circuits. Third, these approaches will be combined by recording neural activity in animals that have been first measured for behavioral preferences to assess which idiosyncratic neural activity signals are predictive of idiosyncratic odor preferences.

为什么每个人的行为会有所不同，这是行为神经科学中一个经久不衰的问题。每个人都是独特的遗传、环境、经历和发展偶然性的产物。这些差异是如何产生个体行为的，目前尚不清楚。本项目旨在使用遗传模型系统Drosophila melanogaster研究行为中的个体起源，该系统允许在个体之间保持遗传，环境和经验恒定。然而，这些实验人群中的气味诱发行为的行为多样性是丰富的。这些个体差异的分子和神经回路机制将使用现代行为神经科学的工具进行研究，包括高通量行为测试，药理学操作，以确定关键的神经调节作用和神经递质，以及成像记录神经活动。初步证据表明，每个人对气味信息的编码方式不同。也就是说，行为差异可能会出现，因为每个人都感觉到不同的嗅觉环境。这些差异的刺激编码的机制将是调查的重点。考虑到动物物种之间分子生物学的共性，所揭示的原理可能也适用于人类。为了广泛传播这些原则，并鼓励学生STEM参与，PI将与冷泉港实验室的DNA学习中心合作，为高中生开发和分发气味偏好套件。这将使学生测量自己的气味偏好的变化，并调查其起源在嗅觉受体的遗传差异。本项目的目的是确定内基因型的差异，气味诱发行为的神经基础使用一个独特的访问系统-早期的嗅觉回路的果蝇，果蝇。在他们实验室开发的工具的基础上，将使用行为和神经生理学表征的组合方法来确定：1）苍蝇气味偏好的特异性程度，2）个体之间气味编码变化的方式，以及3）这种神经生理学变化的行为后果。在苍蝇中，嗅觉系统是粗糙的硬连线，神经元在不同个体之间具有解剖学和遗传学上的可识别性。尽管有这种刻板印象，但个体的气味偏好在苍蝇中是相当可变的-就像人类一样。同样，果蝇对气味的神经编码也各不相同。这些变异维度之间的关系尚不清楚，但可以通过识别预测行为倾向的神经编码特征来阐明。首先，他们的行为分析将扩展到测量个体苍蝇的多维气味偏好。其次，亚细胞分辨率功能成像将量化嗅觉子回路中神经编码的横向变化。第三，这些方法将通过记录动物的神经活动来组合，这些动物首先被测量行为偏好，以评估哪些特异质神经活动信号可以预测特异质气味偏好。